The broad long term objective of this study is to understand how the genetic heterogeneity in populations disposes individuals to hypertensive disorders. Recent advances in molecular genetic technology provides an opportunity to identify the genetic basis of the variation in susceptibility to disease following exposure to environmental agents, including those from food such as fat, sugar, salt, alcohol and tobacco. We propose to identify polymorphisms, both single nucleotide (SNPs) and dinucleotide repeats in the human natriuretic peptide clearance receptor gene (Npr3 because this region or the human genome has recently been implicated in essential hypertension in studies with genetically hypertensive rats. The sequence information will be used to determine if any of these polymorphisms, either alone or in concert with environmental stress factors, cause increase susceptibility to hypertension. Reagents developed in this project will enable one to address the hypothesis: polymorphisms in the Npr 3 gene and surround chromosomal region will be predictive of the pathophysiology of hypertension and related disorders of the cardiovascular system. The specific aims of this proposal are: 1) construct a dense single nucleotide polymorphism map in the Npr gene region. 2) identify the frequencies of recently discovered dinucleotide and tetranucleotide repeat polymorphisms from this region in African- American individuals, 3) use the repeats to search for linked candidate genes with suitable collaborators. 4) develop molecular biological tools and a cell culture system to understand the functional significance of these polymorphisms and their role in the etiology of the disease.